title: Distinguishing between genotoxic and non-genotoxic hepatocarcinogens by gene expression profiling and bioinformatic pathway analysis.
abstract: A rapid and sensitive method to determine the characteristics of carcinogens is needed. In this study, we used a microarray-based genomics approach, with a short-term in vivo model, in combination with insights from statistical and mechanistic analyses to determine the characteristics of carcinogens. Carcinogens were evaluated based on the different mechanisms involved in the responses to genotoxic carcinogens and non-genotoxic carcinogens. Gene profiling was performed at two time points after treatment with six training and four test carcinogens. We mapped the DEG (differentially expressed gene)-related pathways to analyze cellular processes, and we discovered significant mechanisms that involve critical cellular components. Classification results were further supported by Comet and Micronucleus assays. Mechanistic studies based on gene expression profiling enhanced our understanding of the characteristics of different carcinogens. Moreover, the efficiency of this study was demonstrated by the short-term nature of the animal experiments that were conducted.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Korea.
authors.forename: Seul Ji
authors.initials: SJ
authors.lastname: Lee
authors.forename: Young Na
authors.initials: YN
authors.lastname: Yum
authors.forename: Sang Cheol
authors.initials: SC
authors.lastname: Kim
authors.forename: Yuneung
authors.initials: Y
authors.lastname: Kim
authors.forename: Johan
authors.initials: J
authors.lastname: Lim
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Lee
authors.forename: Kyung Hye
authors.initials: KH
authors.lastname: Koo
authors.forename: Joo Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Jee Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Woo Sun
authors.initials: WS
authors.lastname: Lee
authors.forename: Soojung
authors.initials: S
authors.lastname: Sohn
authors.forename: Sue Nie
authors.initials: SN
authors.lastname: Park
authors.forename: Jeong Hill
authors.initials: JH
authors.lastname: Park
authors.forename: Jeongmi
authors.initials: J
authors.lastname: Lee
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Kwon
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D020552:Comet Assay; D019295:Computational Biology; D004249:DNA Damage / Q000187:drug effects; D020869:Gene Expression Profiling; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D046228:Microarray Analysis; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002273:Carcinogens; D009153:Mutagens